Background: In the last several years, commercial pharmacogenetic (PGx) testing for psychotropic medications has become widespread as a means of implementing ?precision medicine?, with some insurers electing to cover the cost of testing. These developments have put increasing pressure on the Veterans Health Administration to implement a mental health focused PGxs program, especially for treating depression, but without sufficient scientific study to support the utility of clinical application. Objectives: We propose a program of research to evaluate the utility of PGx testing in treating Major Depressive Disorder. Methods: Multi-site, randomized clinical trial (n=2000). Patient/provider dyads will be randomly assigned to receive the results of PGx battery either right after randomization (i.e. intervention group) or after 6 months of treatment as usual (i.e. delayed results group). The study will test the following hypotheses: 1. Veterans with MDD whose care is guided by the results of the PGx battery will have a higher rate of remission than those in the delayed results group, as measured by a Patient Health Questionnaire?9 (PHQ-9) score <5. 2. Provider/patient dyads that receive the results of the PGx battery (i.e., the intervention group) will use fewer medications contraindicated by the testing than dyads in the delayed results group. The following subject inclusion and exclusion criteria will be used: Inclusion Criteria. a) age 18 to 80 years, inclusive; b) PHQ-9 score of >10 and a presumptive diagnosis of MDD per PHQ9 criteria; c) at least one prior treatment exposure for MDD (psychotherapy or antidepressant); d) intent to start treatment of the MDD with an antidepressant, and e) willing to provide signed, informed consent to participate in the study. Exclusion Criteria. a) current serious co-occurring psychiatric illness (i.e., schizophrenia, bipolar disorder, psychotic major depression, borderline or antisocial personality disorder, eating disorder; b) current DSM-5 diagnosis of moderate or severe alcohol use disorder; c) current DSM-5 diagnosis of drug use disorder (other than nicotine or cannabis); d) PTSD checklist (PCL-5) score > 39; e) current use of an antipsychotic medication; f) augmentation therapy, e.g., an existing prescription of one or more antidepressants at the time of randomization, exclusive of the index antidepressant prescribed for the current study; trazadone at a dosage of less than 150 mg/day will not be considered augmentation; and f) inpatient hospitalization at the time of consent. Anticipated Impact on Veteran's Healthcare: Despite such a compelling epidemiological imperative, the treatment of depression is often inadequate. As shown now in several studies, to achieve remission from depression, patients and providers must be persistent and try multiple treatments until they find one that is both tolerable and effective. However, with each round of treatment, there is greater attrition from treatment. Replication of the results from the limited PGx implementation studies that have been conducted to date could usher in a new era in the treatment of MDD and provide an impetus for early diagnosis and treatment, resulting in more rapid and higher rates of remission.